NM_004944.4:c.805delC

Variant names:

• chr3-58192799-AG-A
• NM_004944.4:c.805delC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_004944.4(DNASE1L3):​c.805delC​(p.Leu269TrpfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNASE1L3 NM_004944.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.09

Genes affected

DNASE1L3 (HGNC:2959): (deoxyribonuclease 1 like 3) This gene encodes a member of the deoxyribonuclease I family. The encoded protein hydrolyzes DNA, is not inhibited by actin, and mediates the breakdown of DNA during apoptosis. Mutations in this gene are a cause of systemic lupus erythematosus-16. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.123 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-58192799-AG-A is Pathogenic according to our data. Variant chr3-58192799-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3589500.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L3	NM_004944.4	c.805delC	p.Leu269TrpfsTer28	frameshift_variant	Exon 8 of 8	ENST00000394549.7	NP_004935.1
DNASE1L3	NM_001256560.2	c.715delC	p.Leu239TrpfsTer28	frameshift_variant	Exon 7 of 7		NP_001243489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L3	ENST00000394549.7	c.805delC	p.Leu269TrpfsTer28	frameshift_variant	Exon 8 of 8	1	NM_004944.4	ENSP00000378053.2
DNASE1L3	ENST00000486455.5	c.715delC	p.Leu239TrpfsTer28	frameshift_variant	Exon 7 of 7	2		ENSP00000419052.1
DNASE1L3	ENST00000477209.5	c.330delC	p.Trp111GlyfsTer9	frameshift_variant	Exon 4 of 4	2		ENSP00000417976.1
DNASE1L3	ENST00000483681	c.*477delC		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000417047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460198 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal systemic lupus erythematosus type 16 Pathogenic:1

Jun 20, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-58178526;